Resveratrol with systematic name of 3,4′,5-trihydroxystilbene is a known, naturally occurring compound which has gained much interest during the last years in view of its valuable biological properties and pharmacological effects. Resveratrol has been reported to exhibit many therapeutic as well as disease preventive effects including being considered as the reason of the so-called “French Paradox”. The French Paradox is the fact that in people living on a Mediterranean diet, containing high levels of fat and alcohol, an increase to be expected in cancer and heart diseases is not observed. Effects of resveratrol in various cellular and animal assays have been shown, e.g., to inhibit not only skin tumors and leukemia but also platelet aggregation and coagulation. In addition, resveratrol has been shown to be a vasorelaxant, an antimicrobial and fungicidal agent. Recently, data has been published demonstrating that resveratrol is capable of extending the longevity of mice fed a high fat diet.
There have been numerous publications on the synthesis of resveratrol. Chinese patent No.: ZL 200480025470 describes a process for the preparation of resveratrol starting from 3, 5-diacetoxyacetophenone. J. Liu gave an overview of synthesis of resveratrol on August 2007 (see J. Liu, Synthesis of resveratrol and its analogs, phase-transfer catalysed asymmetric glycolate aldol reactions, and total synthesis of 8, 9-methylamido-geldanamycin, Brigham, Department of Chemistry and Biochemistry, Brigham Young University, August 2007). This synthesis process used 3,5-diacetoxyacetophenone. As described therein, “3,5-diacetoxybenzoylchlorides were not explored previously (see line 1 on page 17)”. Based on the inventor's knowledge, currently there is no known publication regarding the process for producing 3,5-diacetoxyacetophenone.
Zhenrong Lu et al. describes a method for synthesis of 3,5-dihydroxyacetophenone by esterification, chlorizating, methylating starting from 3,5-dihydroxybenzoic acid as material, but the overall yield is only 41%. (see Lu, Zhenrong, et al, Study on synthesis of 3,5-dihydroxyacetophenone; Shanxi Chemistry and Industry, March 1998, pages 12-13).
Another known synthesis method involves coupling acyl chlorides with Grignard reagents at room temperature in the presence of the catalyst of tris(acetylacetonate)iron(III), Fe(AcAc)3. But production of 3,5-diacetoxy-acetophenone is not disclosed (see V. Fiandanese, et al, Iron catalyzed cross-coupling reactions of acyl chlorides with Grignard reagents. A mild, general and convenient synthesis of aliphatic and aromatic ketones. Tetrahedron Letters, Vol. 25, No. 42, pp 4805-4808, 1984).
Therefore, considering the importance of multistep synthesis of resveratrol, there is a need in the industry to provide a process for the production of 3,5-diacetoxyacetophenone.